(442h) The Influence of Glycosylation on the Binding of Sars-Cov-2 Spike

Glycosylation is an important posttranslational modification of proteins and plays a crucial role in protein efficacy. It also needs to be understood for optimization of recombinant protein expression. We developed a methodology for modeling glycoproteins with different glycosylation patterns. We use this toolbox to study differently glycosylated 3D structures of the receptor binding domain (RBD) of the spike protein of Sars-Cov-2 in atomistic detail starting from known crystal structures . Computational methods for modeling glycoprotein structures are employed to understand how changes in site-specific oligosaccharide composition and structure influence 3D glycoprotein structure and binding to targets including the Ace2 receptor which again is studied using different glycosylation patterns. We observe e.g. that some ACE2 glycans directly interact with the spike fragment. We also find correlation between glycosylation and the conformation of an ACE2-Fc construct which is a therapeutic candidate. Particularly we find that glycosylation of the fusion protein impacts the average distance between the two major subdomains. Finally we determine the free energy of binding between the RBD and Ace2.